The Clinical Neurophysiology Program (CNP) at UCLA makes use of the unique opportunities provided by an epilepsy surgery facility to carry out direct research on the human brain. In past years, emphasis was placed on clinical research directed toward improving the diagnosis and surgical treatment of epilepsy, although basic research has always been an important part of the program. More recently, resective surgery has become sufficiently accepted as a safe and effective mode of treatment for partial epilepsy to allow clinical activities of the CNP to be supported by hospital funds or supplemented by grants awarded to develop specific diagnostic techniques. Since the beginning of our last renewal, we have requested support only for basic research projects that take advantage of knowledge gained from animal studies and the clinical setting to investigate fundamental mechanisms of normal and abnormal human brain function. Information from patients in our epilepsy surgery facility will be utilized by a multi-disciplinary team of basic and clinical neuroscientists to define anatomical, physiological and metabolic substrates of normal and epileptiform cerebral processes, and to determine how epilepsy-related pathological processes might interfere with normal neuronal integration to disrupt behavior during, and between, seizures. Specifically, we propose to: 1.) examine alterations in cellular morphology and neurotransmitter function in epileptogenic tissue, 2) relate these findings to results of in vivo physiological studies of neuronal activity at the unit level and of spontaneous and stimulation-induced field potentials; 3.) identify aberrant axons and synapses in epileptogenic tissue which may account for hyperexcitability and seizure generation using selective staining, electron microscopy, and in vitro physiological techniques for recording from hippocampal slices; 4.) examine anatomical and physiological substrates of memory and control of cardiorespiratory functions; and 5.) carry out interactive and correlative studies with positron emission tomography to determine if metabolic patterns induced by electrical stimulation of the brain can be used to trace normal and epileptogenic cerebral pathways, and to characterize the functional significance of interictal hypometabolism. The long-term objectives of the CNP are: 1) To reveal cellular and synaptic mechanisms of epileptogenesis in order to suggest new medical, as well as surgical, approaches to antiepileptic therapy; 2.) to better understand the neuronal basis of normal human behavior and mechanisms of pathological disruption that result in abnormal behavior, in order to prevent or more effectively treat behavioral disturbances associated with epilepsy and other neurological disorders; and 3.) to establish the most effective and efficient presurgical evaluation protocol for epileptic patients who are candidates for resective surgery, in order to allow the greatest number of patients to benefit from this procedure.